Retinopathy of prematurity (ROP) is a disorder of development of the neural retina and its vasculature that may impact vision in vulnerable preterm neonates for a lifetime. Clinical care of infants with ROP decreases the likelihood of blindness, but abnormal vision is common, especially in those with disease severe enough to require treatment. Because it has not been possible to distinguish whether disease and/or maldevelopment that affects specific retinal cells and/or the central nervous system (CNS) cause the vision loss, especially when it is less severe, there has been no strategy to prevent subnormal acuity in the majority of infants treated for ROP. The interval that a preterm infant at risk for ROP spends in an intensive care nursery (ICN) is a time of rapid retinal development. Clinicians and researchers do not know how local, CNS and systemic development and disease processes are reflected in the retinal microanatomy. Abnormalities in the retina during infancy are likely early predictors of later vision problems and developmental delay. From study of preterm retinal substructures, brain anatomy, connectivity and functional networks and neuroinflammatory biomarkers this study will elucidate the pathway by which local retinal anatomic changes impact and may predict later subnormal vision and CNS function. The results of this research will enable us to: distinguish ocular from non-ocular contributions to vision loss guide future treatment directed to modify retinal anomalies such as edema; and determine which microanatomic retinal biomarkers are best to monitor effects of ROP, and effects of systemic therapies on the eye and brain. In contrast to indirect ophthalmoscopy or photography, novel non-contact ocular imaging at the bedside would enable direct telemedicine screening for ROP and for neural development in multiple nurseries. Our long-term goal is to help improve preterm infant health care via objective bedside imaging and analysis that characterizes early critical indicators of poor vision, neurological development and ROP. This will rapidly translate t early intervention and improved future vision care. Specific goals of this research are threefold: to implement technological innovations to improve optical coherence tomography (OCT) imaging in non-sedated infants in the ICN; to distinguish elements of retinal microanatomy which predict maldevelopment of visual pathway and poor neurodevelopment that may impact vision in preterm infants; and to delineate which elements and regions (posterior and peripheral) of preterm infant OCT-derived retinal microanatomy best inform us about severity of disease and visual outcomes in infants with ROP. In addition to providing a breakthrough method for bedside analysis of the very preterm (VPT) infant posterior and peripheral retina, this study will provide the pediatric ophthalmologic and telemedicine community with methods to distinguish microanatomic markers that predict infants at risk for abnormal vision, visual pathway injury, poor functional development and progression of ROP (and combinations thereof). These biomarkers will be useful for determining ophthalmic and CNS therapeutic interventions and monitoring their impact on the visual pathway and will thus likely cross over with relevance to other infant eye and brain disease.